Fimepinostat in Treating Brain Tumors in Children and Young Adults
PNOC016
A Target Validation Study of Fimepinostat in Children and Young Adults With Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG), Recurrent Medulloblastoma, or Recurrent High-Grade Glioma (HGG)
3 other identifiers
interventional
30
2 countries
19
Brief Summary
This trial studies how well fimepinostat works in treating patients with newly diagnosed diffuse intrinsic pontine glioma, or medulloblastoma, or high-grade glioma that have come back. Fimepinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for early_phase_1
Started Aug 2019
Longer than P75 for early_phase_1
19 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 26, 2019
CompletedFirst Posted
Study publicly available on registry
March 28, 2019
CompletedStudy Start
First participant enrolled
August 7, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 31, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
August 31, 2027
ExpectedJuly 11, 2025
July 1, 2025
3.2 years
March 26, 2019
July 8, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Penetration of fimepinostat across the blood brain barrier (BBB)
Will be analyzed using descriptive statistics from results of fimepinostat concentrations measured within the tumor tissue collected at the time of a standard of care surgery or biopsy. Within each strata, Simon's two-stage design will be used.
During surgery or biopsy
Study Arms (1)
Treatment (fimepinostat, tumor resection)
EXPERIMENTALPatients receive fimepinostat by mouth once daily, on Days -2 to 0. Within 2 hours of receiving fimepinostat on Day 0, patients undergo tumor resection or biopsy as part of their standard of care. MAINTENANCE PHASE: Patients receive fimepinostat by mouth, once daily for days 1-5 each week. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for up to 12 months from the time treatment begins. Should patients continue to derive clinical benefit, and not experience excess toxicity or progression, patients can continue to receive drug for up to 24 months or longer pending discussion with study chairs and study sponsor.
Interventions
Fimepinostat capsules
Eligibility Criteria
You may qualify if:
- Patients must have one of the following histologically confirmed diagnoses (histologic confirmation from initial diagnosis acceptable, as appropriate):
- Stratum A: Newly diagnosed diffuse intrinsic pontine glioma (WHO grade II-IV) - this stratum does not require tissue confirmation at time of enrollment, but diagnostic confirmation will be required to continue on study after biopsy. Patients with newly diagnosed DIPG will be eligible to enroll before or after standard of care radiation, but must be eligible for a biopsy. Newly diagnosed DIPG stratum should not have received prior therapy before the initiation of fimepinostat, with the exception of those patients who received temozolomide during radiation therapy or who previously received radiation as per standard of care and have not yet undergone a biopsy. All patients who have received therapy other than radiation and temozolomide should be discussed with study chair(s) prior to enrollment. Patients enrolling after standard of care radiation must be enrolled within 14 weeks of completion of radiotherapy.
- Stratum B: Recurrent medulloblastoma (WHO grade IV), any molecular subtype
- Stratum C: Recurrent high-grade glioma (HGG), including anaplastic astrocytoma (WHO grade III) and glioblastoma (WHO grade IV)
- Stratum B \& C: Patients in the recurrent medulloblastoma or recurrent HGG arm can have locally recurrent or disseminated disease, provided resection/biopsy would still be clinically indicated. Disseminated disease can be diagnosed by imaging or Cerebrospinal fluid (CSF) cytology. Recurrent DIPG will be eligible for stratum C; however, eligibility requires biopsy/resection is feasible in a region of tumor outside of the pons (i.e. cerebellar extension or new metastatic site). These patients should be discussed with study chair(s) prior to enrollment
- Patients must be able to swallow intact fimepinostat capsules or mini-tabs without chewing or crushing
- Patients must have body surface area (BSA) \>= 0.5 m\^2
- Patients must undergo tumor tissue collection as part of their standard of care
- Minimum possible tissue collected must be equivalent to about 4-6 stereotactic core biopsies
- Prior Therapy: Patients in the medulloblastoma and HGG strata will be allowed to have undergone prior therapy including surgery, chemotherapy, and radiation therapy. Patients in the newly diagnosed DIPG stratum should not have received prior therapy before the initiation of fimepinostat, with the exception of those patients who received temozolomide during radiation therapy or who previously received radiation as per standard of care and have not yet undergone a biopsy. All patients who have received therapy other than radiation and temozolomide should be discussed with study chair(s) prior to enrollment. Patients must have fully recovered from acute side effects related to previous anti-cancer therapies. Patients undergoing radiation during protocol therapy will not be permitted to receive other concomitant agents with radiation and pending initiation of maintenance with fimepinostat
- Myelosuppressive chemotherapy: At least 21 days after last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
- Hematopoietic growth factors: At least 14 days after last dose of a long-acting growth factor or 7 days after short-acting growth factor or beyond time during which adverse events are known to occur
- Biologic (anti-neoplastic agent): At least 7 days after last dose of a biologic agent or beyond time during which adverse events are known to occur
- Monoclonal antibodies: At least 21 days after last dose of monoclonal antibody
- Radiotherapy:
- +28 more criteria
You may not qualify if:
- Subjects who have not recovered from acute adverse events due to therapeutic agents administered more than 4 weeks earlier
- Patients must not have received prior therapy with single-agent or combination histone deacetylase (HDAC) and Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) inhibitors
- Subjects who are receiving any other investigational agent
- History of allergic reaction to compounds of similar chemical or biological composition to fimepinostat
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements
- Patients with active human immunodeficiency virus (HIV) infection and with potential life-threatening consequences associated with immune-suppressive therapy
- Patients with history of type 1 or 2 diabetes mellitus
- Patients with gastrointestinal condition that could interfere with absorption or metabolism of fimepinostat
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Sabine Mueller, MD, PhDlead
- Pediatric Neuro-Oncology Consortiumcollaborator
- Cannonball Kids' Cancer Foundationcollaborator
- Curis, Inc.collaborator
Study Sites (19)
Children's Hospital Los Angeles (CHLA)
Los Angeles, California, 90027, United States
Rady Children's Hospital
San Diego, California, 92123, United States
University of California, San Francisco
San Francisco, California, 94143, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
University of Florida
Gainesville, Florida, 32611, United States
Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611, United States
Johns Hopkins Hospital
Baltimore, Maryland, 21231, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
University of Michigan Hospital
Ann Arbor, Michigan, 48109, United States
Children's Minnesota Research Institute
Minneapolis, Minnesota, 55404, United States
Washington University in St Louis
St Louis, Missouri, 63110, United States
Nationwide Children's
Columbus, Ohio, 43205, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia (CHOP)
Philadelphia, Pennsylvania, 19146, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
University of Utah, Children's Primary
Salt Lake City, Utah, 84113, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
The University Children's Hospital in Zurich
Zurich, Canton of Zurich, 8032, Switzerland
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sabine Mueller, MD, PhD
University of California, San Francisco
Study Design
- Study Type
- interventional
- Phase
- early phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
March 26, 2019
First Posted
March 28, 2019
Study Start
August 7, 2019
Primary Completion
October 31, 2022
Study Completion (Estimated)
August 31, 2027
Last Updated
July 11, 2025
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
Individual participant data after de-identification